Efficacy and tolerability of daily-half dose linezolid in patients with intractable multidrug-resistant tuberculosis
Efficacy and tolerability of daily-half dose linezolid in patients with intractable multidrug-resistant tuberculosis
复制标题
DOI：
10.1093/jac/dkl298
复制
发表时间：
2006-09-01
影响因子：
5.2
通讯作者：
Shim, Tae Sun
中科院分区：
文献类型：
--
作者：
Park, I-Nae;Hong, Sang-Bum;Shim, Tae Sun
目的：尽管利奈唑胺对结核分枝杆菌具有良好的体外活性，但其长期用于治疗耐多药结核病（MDR-TB）可能受到其成本和严重不良反应的限制。因此，我们评估了减少剂量的利奈唑胺与其他抗结核药物联合治疗难治性或广泛性耐多药结核病患者的疗效和耐受性。方法：对至少3个治疗周期无反应的耐多药结核病患者接受每日一半剂量的利奈唑胺治疗结果：截至2006年3月，8例患者，所有HIV阴性，已与利奈唑胺治疗3-18个月。所有患者的培养结果平均在82天内变为阴性。4名患者出现周围神经病变，2名患者出现视神经病变，1名患者出现贫血。虽然停止利奈唑胺治疗后视神经病变消退，但周围神经病变仍持续。1例患者完成了18个月的利奈唑胺治疗。2例患者已服用利奈唑胺15-17个月，仍在接受治疗并保持培养转化。3名患者在7-9个月后停用利奈唑胺，其中2名是因为副作用，1名是因为经济原因，但仍在接受其他二线药物治疗并进行培养转化。两名患者死于严重的呼吸衰竭，但以前都表现出文化conversion.Conclusions：虽然每天一半剂量的利奈唑胺是有效的难治性或广泛的耐多药结核病患者，这种剂量方案并没有减少长期使用相关的副作用，如周围和视神经病变。
Objectives: Although linezolid has good in vitro activity against Mycobacterium tuberculosis, its long-term use in the treatment of multidrug-resistant tuberculosis (MDR-TB) may be limited by its cost and serious adverse reactions. We therefore evaluated the efficacy and tolerability of a reduced dose of linezolid, in combination with other anti-TB drugs, in patients with intractable or extensive MDR-TB.Methods: MDR-TB patients unresponsive to at least three cycles of treatment were treated with daily-half doses of linezolid (600 mg once per day) plus at least four companion drugs.Results: As of March 2006, eight patients, all HIV-negative, had been treated with linezolid for 3-18 months. Cultures became negative in all patients in an average of 82 days. Four patients developed peripheral neuropathy, two developed optic neuropathy and one developed anaemia. Although optic neuropathy resolved after cessation of linezolid therapy, peripheral neuropathy continued. One patient completed 18 months of linezolid therapy. Two patients, who have taken linezolid for 15-17 months, are still on treatment and remain in culture conversion. Three patients stopped linezolid after 7-9 months, two because of side effects and one for economic reasons, but remain on treatment with other second-line drugs with culture conversion. Two patients died from severe respiratory failure, but both previously had shown culture conversion.Conclusions: Although daily-half doses of linezolid were effective in patients with intractable or extensive MDR-TB, this dosage regimen did not reduce long-term use-related side effects, such as peripheral and optic neuropathy.